Background: Humerus shaft fracture accounts for 20% of all humeral fractures. Comminuted fracture of humerus requires great surgical skill to obtain stable fixation. The aim was to study the effect of locking compression plate (LCP) in the fixation of comminuted diaphyseal humerus fracture. Materials and Methods: This is a prospective study done over 12 months in which 30 consecutive skeletally mature, closed diaphyseal comminuted humerus fractures underwent fixation with LCP and outcome evaluated in terms of radiological evidence of healing, functional outcome, and complications if any. Results: Union of all thirty fractures was achieved primarily. There was no implant-related complication. The mean Mayo Elbow Performance Score at 6-month follow-up was 90.5, while the mean University of California and Los Angeles score (UCLA) at 6-month follow-up was 29.66 with minimum 24 to maximum of 34. Conclusions: Internal fixation of comminuted diaphyseal humeral fractures with locking plates described in this study allows an intensive program of rehabilitation immediately after surgery and is associated with a high union rate.